Lipases is a group of enzymes taking part in the digestion of fat by hydrolysing lipids present in the food thereby allowing absorption of the fat by the intestinal tract. The lipases are mainly three, viz gastric lipase, pancreatic lipase and carboxylic ester lipase.
Pancreatic lipase is the main enzyme responsible for the hydrolysis of triacylglycerols in the diet. The pancreatic lipase is a typical lipase catalysing the hydrolysis of water-insoluble substrates forming an interface. The enzyme is said to be activated by interfaces.
The most peculiar property of lipase is that the activity is strongly inhibited by surface active agents like the naturally occurring bile salts. To overcome this nature has come to use another pancreatic protein, colipase.
Colipase binds to lipase in a 1:1 molar ratio and also binds to the bile-salt covered triacylglycerol interface in this way anchoring lipase to its triacylglycerol substrate. Colipase as such has no lipolytic activity.
Colipase is formed by pancreas and is excreted as a procolipase.
It has been established that mice deficient in procolipase and fed a high fat diet will have cholesterol, triglyceride, glucose and insulin concentrations in blood serum at about the same levels as mice fed on low fat diet. (D'Agostino, D. et al., J. Biol. Chem. vol 277, no. 9, pp 7170-7177 (2002)).
Obesity has in recent days become an ever increasing problem to population of the industrialized world, whereby e.g., the average weight of a male at the age of 20 has increased with about 10 kilogrammes during the last 20 years. Obesity leads to the formation of the so-called metabolic syndrome, to which diabetes and cardio-vascular diseases belong. The worst forms of obesity are visceral fat accumulation, liver fat accumulation and even muscular fat accumulation.
The high fat intake or over intake of fat is due to a number of factors, such as too much sitting still, too much of fat rich food (so called “junk food”), and an erroneous diet information. It is also a relic of old days tradition of having a large calorie intake due to a heavier workday.
Food of today does not provide a long-term feeling of satisfaction either, which in turn leads to an increased food intake. However, a lipid diet remaining in the intestine will increase the feeling of satisfaction for a longer time period, and thus there is a desire having lipids remaining in the intestines to satisfy the demand from the brain. One way of preventing obesity is by administering a preparation under the trademark XENECAL®, which is a lipase inhibitor in general.
U.S. Pat. No. 4,588,843 discloses a synthesis of (alkoxyalkyl)amines, whereby the compound explicitly prepared is 2-(dimethylamino)ethyl dodecyl ether. The compound is said to have a use as an intermediate for lubricating oil additives, such as detergent-dispersants and pour point depressants, soap and detergent products, such as surface active agents, and foam stabilizers, extenders for polymers, such as polyurethanes and epoxy resins, agricultural chemicals, such as herbicides, fungicides, plant growth regulators, insecticides, vermicides, miticides, and the like. No pharmaceutical use is proposed.
The main object of the present invention is to provide a therapeutically active compound which inhibits pancreatic lipase-colipase action, thereby reducing digestion of lipids from the diet, thereby preventing obesity in general by reduced lipid absorption.
Another object is to obtain a situation in the intestines where diet lipid/fat remains in the intestines providing a basis for a better feeling of satisfaction, thereby avoiding an over-intake of food.